Non-Hodgkin's Lymphoma is a group of lymphoid malignancies classified into sub-groups based on histological appearance, biology and clinical presentation/course. In 2002 there were approximately 54,000 new cases of NHL in the US, representing 4% of all cancers (Ries et al., 2002). The annual incidence rate was 19.1 cases per 100,000 people. Most NHL cases arise in the lymph node (70-80%). Currently, there is an increased incidence of NHL in the US of 2.6% per year in males and 2.0% per year in females. Immunodeficiency (both acquired and congenital) is the strongest risk factor known to increase NHL (Rabkin et al., 1997).
Cytogenetic studies have shown that some histological and immunological sub-types of NHL have chromosomal abnormalities with reciprocal translocations, frequently involving genes for the B-cell receptor and an oncogene. Lymphomagenesis results in clonal expansion of the transformed B-cell, with each daughter cell expressing the B-cell receptor (BCR) on the cell surface as well as BCR-derived peptides associated with MHC class I and II molecules. The BCR has a unique conformation formed by the hypervariable regions of the heavy and light chain, this is referred to as the “idiotype,” is the same for every daughter cell within the tumor, and is not present on significant numbers of normal cells. Therefore, the idiotype is a specific tumor antigen and a target for lymphoma therapy.
The follicular lymphomas are the most common subtype of indolent NHL, representing about 30% of NHL. Rituximab, a chimeric anti-CD20 antibody originally studied in patients with relapsed and refractory follicular low-grade NHL, exhibits a high overall response rates as an initial therapy, but a limited response duration. In addition, idiotype-based clinical trials for follicular NHL have been successful in the setting of minimal residual disease, increasing disease free survival as well as molecular remission. A current idiotype-based vaccine for B-NHL uses KLH as a protein carrier coupled to the patient's own B cell receptor (BCR) idiotype (Id) and GM-CSF as an adjuvant. Patients who respond to the Id-KLH vaccine with an anti-idiotype response (50-70%) exhibit higher rates of disease-free survival.
Improved therapies for NHL continue to be needed in the art.